This application is a request for renewal of our R01 entitled: "A proliferative switch for genetically modified cells," which was funded beginning in August 1997. The stated goal of that application was "to apply newly developed technology to the expansion of genetically modified hemopoietic cells in vitro or in vivo." We have achieved that goal. Our approach uses a derivative of the thrombopoietin receptor (mpl) that delivers a conditional growth signal in response to a drug called a chemical inducer of dimerization (CID). In specific aim 1 we will humanize the mpl vector. In specific aim 2 we will test our humanized vector in normal mice and in a mouse model of mpl deficiency. In specific aim 3 we will test the humanized vector in a canine model. in specific aim 4 we will test the humanized vector in hemopoietic cells taken from patients with mpl deficiency.